Overall objctives are to define changes that occur in the types and quantities of enzymes in cells of the hemopoietic system during normal differentiation and as a result of genetic mutation or neplastic transformation. The activities of DNA dependent DNA polymerases, terminal riboadenylate transferase, and terminal deoxyriboadenylate transferase are being measured in human bone marrow, cells of peripheral blood, and during human lymphocyte activation in culture. The purpose of this part of the project is to define the activities of enzymes that are important in nucleic acid metabolism in differentiating hemopoietic cells. A second line of investigation is a study of enzyme defects in red cell metabolism, which resul in congential nonspherocytic hemolytic anemias. Patients from three different families are under study, which includes an evaluation of the clinical manifestations of the enzyme defect as well as definition of the effect of the mutation upon the metabolism of the cell.